Protocols involving prisoners must be approved by OHRP
Some say new guidance complicates things
In an attempt to clarify Department of Health and Human Services’ (HHS) regulations, the federal Office of Human Research Protections (OHRP) has issued an update to its 2000 guidance on research involving prisoners.
The new document contains mostly changes in numbering and format, but also clarifies certain responsibilities of institutional review boards (IRBs) and research institutions under 45 CFR 46, subpart C — the section of federal DHHS regulations that specifically cover the use of prisoners as subjects in research trials, says Karenna Cooper, public health analyst with the OHRP’s Division of Policy Planning and Special Projects, and the Office’s designated prisoner research contact person.
In particular, the new guidance clarifies that research institutions must wait to receive written approval for protocols or amended protocols involving incarcerated persons, before proceeding, she says. And in addition to a certification letter, a copy of the proposed research protocol must be submitted to OHRP for review.
For example, when sending the letter certifying that the seven qualifying conditions listed under subpart C have been met, the institution must wait for formal approval.
"HHS conducted or sponsored research involving prisoners as subjects may not proceed until OHRP issues its approval in writing to the institution," Cooper explains. "This is not a new policy, but the first time that it has been explicitly explained that OHRP will be writing a letter back to the institution and that the involvement of prisoners must wait until the institution gets the letter."
The institution must now also submit a copy of the research proposal to the OHRP so that the office can determine whether the proposed research involves one of the categories of permissible research under the HHS regulations, she adds.
"Before, all they had to submit was a certification letter containing a brief summary," she explains. "Now they must submit a certification letter and research proposal."
Improved protections for prisoners?
Some investigators, however, feel the new OHRP guidance shows little improvement over the 2000 document and continues to complicate research that involves prisoners without adding any important protections.
The requirement that OHRP review proposed research protocols is unnecessary; And the office’s insistence that protocols be amended when previously unincarcerated participants become prisoners is having the unintended consequence of excluding many ill prisoners for whom clinical research trials may be the best hope of helping, says Charles R. McCarthy, PhD, senior research fellow at the Kennedy Institute for Ethics at Georgetown University, and the former director of the HHS’ Office for Protection for Research Risks (OPRR, the office that is now the OHRP).
"IRBs now are trained to review and approve such studies without the additional requirement of HHS review," he states. "IRBs that lack experience can easily network with experienced IRBs and easily obtain advice and guidance from OHRP. The HHS layer of review no longer offers any important protection for prisoner subjects."
And the guidance requiring that all applicable conditions of 45 CFR subpart C apply to persons already enrolled in trials prior to imprisonment was neither foreseen nor recommended by the National Commission for the Protection of Human Subjects of Biomedical or Behavioral Research, upon whose findings the current federal regulations are based.
"This added requirement places heavy burdens on principal investigators [PIs] and heavy burdens on IRBs and their support staffs," McCarthy explains. "Yet, it offers little if any additional protection to subjects And in some cases, it may be harmful to subjects."
Background on regulations
In 1978, the National Commission for the Protection of Human Subjects of Biomedical or Behavioral Research issued a report finding that — between 1974 and 1977 — large numbers of drug trials were conducted in prisons for reasons of convenience, mainly, that prisoners provide a stable cohort of subjects.
The commission further found that living conditions in most prisons were poor and they believed many prisoners faced undue pressure to participate in research as a means of obtaining some relief from deplorable living conditions, McCarthy explains.
Because overall prison reform was out of its jurisdiction, the HHS issued specific regulations requiring that prisoners receive no privileges or benefits for participation in research that were not accorded to other prisoners.
The effect of those regulations has been profound, McCarthy says.
For many years, little, if any, research has been conducted in prisons that could be performed in freestanding communities.
The kinds of research now conducted in prisons fall into two major categories: 1) behavior and social science studies into the behaviors of prisoners that led to incarceration; and 2) research into diseases or conditions that affect prisoners in higher proportion than they do members of freestanding communities.
Although studies in the first category seldom offer benefits to individual subject participants, they are usually low-risk studies that offer benefits to prisoners as a class, McCarthy says.
Studies in the second category, however, almost always offer the prospect of a direct benefit to the prisoner subjects, he notes.
"Even if subjects serve on the placebo arm of a study, they are nearly always provided — when the trial is finished — with beneficial treatments if the study justifies such treatments."
Although only a small percentage of research of any kind is conducted in prisons, most of the studies conducted there hold out the prospect of direct benefit to prisoners in some way, he adds.
"In a few cases, it offers the prisoners their only hope," McCarthy maintains. "Research involving prisoners may not be important for breakthrough new knowledge, But nevertheless, a few research studies are of critical — life and death — importance for prisoners."
Guidance adds burden
The OHRP requirement that investigators amend study protocols when subjects become prisoners is particularly problematic for researchers and often leads to the exclusion of subject participants who could benefit from research, McCarthy continues.
"The new prison environment could not possibly affect the subject’s initial consent," he explains. "The only protection included is that there is a slight chance that it could protect the freedom of a subject’s decision to continue or not continue in a study."
To illustrate his point, McCarthy provides the following example based on his own experience:
"A PI receives an NIH grant to conduct HIV/ AIDS research. Recruitment of subjects is limited to persons who are HIV-positive or who are suffering from AIDS," McCarthy states. "Subjects who consent to participate are to be randomized into group A, which will receive standard treatment, and group B, which will receive standard treatment plus an experimental drug. It is known in advance that many of the potential subjects have a history of drug abuse and/or promiscuous sexual behavior. An IRB carefully reviews and approves the study. Within a month, one of the subjects is arrested for possession of an illegal substance and is incarcerated in the city jail awaiting trial.
The PI notifies the IRB that a subject has been incarcerated but requests that the subject be allowed to continue, documenting that the study in the best interests of the subject.’ The IRB approves the continuation. The PI then submits an amended protocol to the IRB asserting that all seven required conditions in the regulations are met in the city jail.
The amended protocol is approved by the IRB and forwarded to HHS for final approval. The subject is held in jail for six weeks and then the case is dismissed for lack of evidence. HHS has not yet acted on the approval that is no longer needed. In the meantime another subject is arrested by state police for transporting illegal drugs across state lines, and is held in one of the state prisons. The PI must now amend the protocol again to show that all seven conditions are met in the state prison.
Two months later, the IRB approves the amended protocol and it is forwarded to HHS for final approval. The case is tried, the defendant is found guilty, but because the state prison is overcrowded the prisoner is sent to a state prison in another state. Now, the PI must amend the protocol once more and verify the seven conditions for the out-of-state prison. This takes much longer because the PI is unfamiliar with the procedures in another state.
In the meantime, HHS has approved the continuation of the prisoner in the local state prison — But of course, the prisoner is elsewhere. This time, the PI decides that many days of work have been spent on meeting conditions that changed before they could be finally approved. The PI notifies the subject that he is dropped from the study. The subject no longer receives the standard treatment or standard treatment plus an experimental treatment.
The subject applies for Medicaid treatment in a state in which he lacks permanent residency. Long delays occur while his Medicaid request is adjudicated. In the meantime, he receives only emergency treatment of a deadly disease. The PI says, Next time I will drop from the study any subject who is incarcerated because I cannot give all my time to complying with the OHRP Guidance and dealing with the IRB and with HHS.’ The subject’s opportunity to participate in beneficial research has been lost."
In that situation, it is hard to believe that his rights have been protected by 45 CFR 46 Subpart C as interpreted by the 2000 or the 2003 documents, McCarthy says.
The purpose of the regulation, in many cases, is, in effect, undermined by the OHRP guidance, he adds.
Need for pubic comment, broader perspective
The OHRP has given an interpretation of the federal regulations that was not addressed by the National Commission, on which the federal regulation was based, McCarthy stresses.
The OHRP also does not have staff members with that expertise in prison research that it requires of all IRBs that oversee research involving prisoners, he adds.
To truly design a guidance that is helpful to researchers and protects incarcerated subjects, the office should seek input from members of the committee that drafted the federal regulations after hearing public comments and seek public comment of any draft guidance that they publish, he notes.
"The guidance provided in 2000 failed to provide much historical background on the work of the National Commission," McCarthy concludes. "Although the guidance provided several quotations from the preamble to the regulations — it provided little information about the reasons why the commission made the recommendations upon which the regulations are based."
Regulations cause problems when the reasons for the regulations are no longer understood, he contends.
"As a result IRBs and PIs found themselves forced to carry out procedures that made little sense to them," he says. "Instead of promoting a climate of compliance within research institutions, the guidance simply discourages PIs from including subjects who might become incarcerated and encouraged PIs to discontinue research involving already enrolled prisoner subjects rather than revise protocols and wait long periods of time — often more than a year — for HHS approvals of protocols already approved by IRBs."
(Editor’s note: Information on the OHRP guidance, and copies of the document, can be found on the web at: http://ohrp.osophs.dhhs.gov/. Click under the heading, "News.")
In an attempt to clarify Department of Health and Human Services (HHS) regulations, the federal Office of Human Research Protections (OHRP) has issued an update to its 2000 guidance on research involving prisoners.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content